The prostate is the most common non-cutaneous cancer site in males in developed countries. It is the second most common cause of death from cancer in men aged 60 or older. Early detection methods, such as prostate specific antigen (PSA) testing and digital rectal exam (DRE), have been developed. PSA is a glycoprotein secreted by the prostate gland. However, the PSA test has limitations of sensitivity and selectivity. In general, PSA levels above 4 ng/mL are suggestive of cancer and levels above 10 ng/mL are highly suggestive. However, many individuals with elevated levels do not have prostate cancer, but exhibit benign prostatic hypertrophy. Conversely, many persons with prostate cancer have normal PSA levels at the time of diagnosis. In addition, while it is known that genetic factors are involved in the development of prostate cancer, few genes with a direct role in prostate cancer have been identified.
Considerable evidence demonstrates that inherited genetic variants or mutations predispose individuals to developing prostate cancer. Germline mutations are estimated to account for approximately 9% of all prostate cancers and 45% of cases in men under age 55. Numerous linkage-mapping studies have identified candidate regions throughout the genome that may contain genes that predispose to prostate cancer. However, the majority of sequence variants within these regions that cause disease have not yet been identified. Identification of genetic sequences that are linked to prostate cancer allows determination of those with a higher risk of developing prostate cancer. Such information can be used to monitor those individuals with higher prostate cancer risk more closely, thereby allowing opportunity to detect prostate cancer at an early stage, which increases the likelihood of survival.
Therefore, there is a continuing need for determining which patients are at risk of developing prostate cancer.